Potassium Hydroxide → 9-Benzyl-6-hydroxy-3-oxa-9-azabicyclo[3.3.1]nonan-7-one

HRID 1778518Notes

Reaction equation

HRID 1778518 reaction equation
[OH-].[K+].[CH2:3]([N:10]1[CH:15]2[CH2:16][C:17](=[O:19])[CH2:18][CH:11]1[CH2:12][O:13][CH2:14]2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C(OI(C1C=CC=CC=1)OC(=O)C)(=[O:22])C>CO>[CH2:3]([N:10]1[CH:11]2[CH:18]([OH:22])[C:17](=[O:19])[CH2:16][CH:15]1[CH2:14][O:13][CH2:12]2)[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1

Participants

5

Reactant 3

HCID 14797Potassium HydroxideHCID 76724Iodobenzene diacetateHCID 156391149-Benzyl-3-oxa-9-azabicyclo(3.3.1)nonan-7-one

Product 1

HCID 1176974359-Benzyl-6-hydroxy-3-oxa-9-azabicyclo[3.3.1]nonan-7-oneYield 25%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent3×

Conditions

Temperature
0 °C

Procedure

To a stirred solution of potassium hydroxide (730 mg, 13 mmol) in dry MeOH (50 mL) at 0° C. under nitrogen was added a solution of 9-benzyl-3-oxa-9-azabicyclo[3.3.1]nonan-7-one (CAS: 81514-40-1, 1 g, 4.3 mmol) in dry MeOH (20 mL) dropwise over 10 min. The reaction mixture was stirred at 0° C. for another 10 min, and PhI(OAc)2 (1.83 g, 5.5 mmol) was added portion wise over 10 min. The reaction mixture was warmed to room temperature, with stirring, overnight. After the starting material disappeared as monitored by TLC, MeOH was removed under reduced pressure and the residue was cooled to 0° C. and 10 ml of 6N HCl was added carefully. The mixture was stirred at room temperature for 2 hours, and then ethyl acetate and water (50 mL, 1:1) were added. The aqueous layer was separated and was added into K2CO3 till the solution was saturated. The mixture was extracted with ethyl acetate (20 mL) three times, dried and concentrated, the residue was purified by silica gel (EA/PE=1:2) to give 9-benzyl-6-hydroxy-3-oxa-9-azabicyclo[3.3.1]nonan-7-one 106b as colorless oil, 270 mg, yield: 25%. MS: calc'd (MH+) 248, measured (MH+) 248.

Workup

  1. temperatureThe reaction mixture was warmed to room temperature
  2. stirringwith stirring, overnight
  3. customwas removed under reduced pressure
  4. temperaturethe residue was cooled to 0° C.
  5. addition10 ml of 6N HCl was added carefully
  6. stirringThe mixture was stirred at room temperature for 2 hours
  7. additionethyl acetate and water (50 mL, 1:1) were added
  8. customThe aqueous layer was separated
  9. additionwas added into K2CO3 till the solution
  10. extractionThe mixture was extracted with ethyl acetate (20 mL) three times
  11. customdried
  12. concentrationconcentrated
  13. customthe residue was purified by silica gel (EA/PE=1:2)

Sources & evidence

ORD record
ord-e842c3c0bded47f38616a0398ebd5b9f
Source dataset
uspto-grants-2016_02
Patent number
US09266904B2

Reaction notes

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